With ferric sulfate nonahydrate In water at 80℃; for 24 h;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
8
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 1455-77-2 ]
[ 120-89-8 ]
[ 849585-22-4 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 71-30-7 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 56-06-4 ]
[ 66224-66-6 ]
[ 57-13-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
[ 18588-61-9 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
9
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 1455-77-2 ]
[ 120-89-8 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 71-30-7 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 66224-66-6 ]
[ 57-13-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
10
[ 77287-34-4 ]
[ 23147-58-2 ]
[ 1455-77-2 ]
[ 120-89-8 ]
[ 849585-22-4 ]
[ 73-40-5 ]
[ 110-15-6 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 57-13-6 ]
[ 302-72-7 ]
[ 18588-61-9 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
11
[ 4553-62-2 ]
[ 110-15-6 ]
[ 123-56-8 ]
[ 29553-51-3 ]
Yield
Reaction Conditions
Operation in experiment
96 %Chromat.
With phosphoric acid In water at 270℃; for 2 h;
Example 5 Preparation of a Mixture of Imides From Pure MGN and From Bio-Sourced Succinic Acid [0169] In a 100 mL reactor, are introduced 23 g of 2-methyl-glutaronitrile and then 25 g of succinic acid obtained by fermentation are added. Stirring is applied and 0.1 g of 85percent ortho-phosphoric acid are added. The reaction medium is heated up to 270° C. and these conditions are maintained for 2 hours. By GC analysis, the following results are obtained: [0170] TT percent (MGN)=98percent [0171] RR percent (MGI)=96percent [0172] RR percent (succinimide)=97percent
Reference：
[1] Doklady Akademii Nauk SSSR, 1955, vol. 102, p. 113,115[2] Chem.Abstr., 1956, p. 4899
13
[ 110-15-6 ]
[ 72-14-0 ]
[ 116-43-8 ]
Reference：
[1] Journal of the American Chemical Society, 1942, vol. 64, p. 1572,1573, 1574
14
[ 77287-34-4 ]
[ 23147-58-2 ]
[ 1455-77-2 ]
[ 849585-22-4 ]
[ 328-42-7 ]
[ 110-15-6 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 66-22-8 ]
[ 56-06-4 ]
[ 57-13-6 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
15
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 1455-77-2 ]
[ 120-89-8 ]
[ 849585-22-4 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 71-30-7 ]
[ 120-73-0 ]
[ 144-62-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 56-06-4 ]
[ 66224-66-6 ]
[ 57-13-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
[ 18588-61-9 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
16
[ 77287-34-4 ]
[ 51953-18-5 ]
[ 120-89-8 ]
[ 73-40-5 ]
[ 328-42-7 ]
[ 110-15-6 ]
[ 144-62-7 ]
[ 127-17-3 ]
[ 56-06-4 ]
[ 57-13-6 ]
[ 18588-61-9 ]
[ 18514-52-8 ]
Reference：
[1] Chemistry - A European Journal, 2018, vol. 24, # 32, p. 8126 - 8132
17
[ 13357-09-0 ]
[ 110-15-6 ]
[ 443-48-1 ]
[ 13182-87-1 ]
Reference：
[1] European Journal of Medicinal Chemistry, 1998, vol. 33, # 9, p. 675 - 683
18
[ 220819-20-5 ]
[ 130-26-7 ]
[ 110-15-6 ]
[ 443-48-1 ]
[ 13182-87-1 ]
Reference：
[1] Scientia Pharmaceutica, 1998, vol. 66, # 4, p. 309 - 324
19
[ 220819-23-8 ]
[ 83-73-8 ]
[ 110-15-6 ]
[ 443-48-1 ]
[ 13182-87-1 ]
Reference：
[1] Scientia Pharmaceutica, 1998, vol. 66, # 4, p. 309 - 324
20
[ 77287-34-4 ]
[ 156-81-0 ]
[ 849585-22-4 ]
[ 617-48-1 ]
[ 2491-15-8 ]
[ 110-15-6 ]
[ 108-53-2 ]
[ 71-30-7 ]
[ 113-00-8 ]
[ 127-17-3 ]
[ 66-22-8 ]
[ 66224-66-6 ]
[ 56-40-6 ]
[ 302-72-7 ]
[ 18514-52-8 ]
Yield
Reaction Conditions
Operation in experiment
0.18 mg
With ferric sulfate nonahydrate In water at 80℃; for 24 h;
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
General procedure: To model the chemical environment on the outer side of thetubular structures, NH2CHO (200 μL) was mixed with thesodium silicate solution (2.0 mL) in the presence of preformedMSH [ZnCl2, FeCl2·4H2O, CuCl2·2H2O, Fe2(SO4)3·9H2O,and MgSO4] (2.0percent w/w) at 80 °C for 24 h. In two selectedcases [FeCl2 and Fe2(SO4)3·9H2O], NH2CHO (200 μL) wasmixed with the sodium silicate solution (2.0 mL) in the presence of selected growing MSH (starting from 2.0percent w/w ofthe corresponding salt’s pellet) at 80 °C for 24 h. For the innerenvironment, NH2CHO (200 μL) was mixed with distilledwater (2.0 mL) in the presence of selected MSH (2.0percent w/w) at80 °C for 24 h. The reaction of NH2CHO (10percent v/v) with thesodium silicate solution (pH 12) without MSH membranes wasalso analyzed under similar experimental conditions. Theproducts were analyzed by gas chromatography associatedwith mass spectrometry (GC-MS) after treatment with N,Nbis-trimethylsilyl trifluoroacetamide in pyridine (620 μL) at 60°C for 4 h in the presence of betulinol (CAS Registry Number473-98-3) as the internal standard (0.2 mg). Mass spectrometrywas performed by the following program: injection temperature280 °C, detector temperature 280 °C, gradient 100 °C for 2min, and 10 °C/min for 60 min. To identify the structure of theproducts, two strategies were followed. First, the spectra werecompared with commercially available electron mass spectrumlibraries such as NIST (Fison, Manchester, U.K.). Second, GCMSanalysis was repeated with standard compounds. Allproducts have been recognized with a similarity index (SI)greater than 98percent compared to that of the reference standards.The analysis was limited to products of ≥1 ng/mL, and theyield was calculated as micrograms of product per startingformamide. For further experimental details, see the SupportingInformation.
Reference：
[1] J. Gen. Chem. USSR (Engl. Transl.), 1963, vol. 33, p. 919 - 922[2] Zhurnal Obshchei Khimii, 1963, vol. 33, p. 934 - 938
35
[ 110-15-6 ]
[ 100-51-6 ]
[ 103-50-4 ]
[ 103-43-5 ]
[ 103-40-2 ]
Reference：
[1] Russian Journal of General Chemistry, 2008, vol. 78, # 10, p. 1920 - 1923
36
[ 110-15-6 ]
[ 123-11-5 ]
[ 43212-67-5 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1948, p. 567,569
[2] Journal of the American Chemical Society, 1949, vol. 71, p. 633,637
37
[ 67-56-1 ]
[ 124-41-4 ]
[ 123-25-1 ]
[ 110-15-6 ]
[ 6289-46-9 ]
Reference：
[1] Monatshefte fuer Chemie, 1911, vol. 32, p. 77
38
[ 1492-23-5 ]
[ 110-15-6 ]
[ 2185-03-7 ]
Yield
Reaction Conditions
Operation in experiment
1.2 g
at 50℃; for 2 h;
2 g (9.12 mmol) of O-succinyl-L-homoserine was dissolved in 10 ml (120 mmol, 13.2 equivalents) of concentrated hydrochloric acid, and the solution was allowed to react at 50° C. for 2 hours, and then cooled at room temperature for 3 hours. The precipitated solid was filtered, thereby obtaining 0.7 g (5.9 mmol) of succinic acid (SA) crystal (purity: 65percent). The filtrate was concentrated and recrystallized with anhydrous ethanol to yield 1.2 g (8.72 mmol) of homoserine lactone hydrochloride (purity: 95percent). 1H NMR (300 MHz, DMSO) δ 8.83 (2H, brs), 4.46 (1H, t, J=8.8 Hz), 4.36-4.24 (2H, m), 2.61-2.51 (1H, m), 2.30 (1H, t, J=10.3 Hz): Homoserine lactone hydrochloride 1H NMR (300 MHz, D2O) δ 4.36 (1H, t, J=9.0 Hz), 4.29 (2H, q, J=9.0 Hz), 2.69-2.60 (1H, m), 2.36-2.21 (1H, m): Homoserine lactone hydrochloride 1H NMR (300 MHz, D2O) δ 2.47 (4H, s): Succinic acid
The 40.50g (0.15mol) of doxylamine and 17.7g (0.15mol) of succinic acid was added 250ml flask and 130ml of acetone was heated at reflux until the solid dissolved, stirring was continued 1H; The acetone was distilled off and then 80ml of isopropyl propyl ether, ultrasound 10min, remove the upper isopropyl ether, spin dry and add 80ml of acetone, stirred at 0 °C crystallization, filtration to give the crude product. The crude product was recrystallized twice from acetone (crude 1g: Acetone 1.2ml), 80percent yield, with a purity of 99.88percent, the largest single hetero 0.07percent.
181.8 g
at 60℃;
The step S1 prepared 136g of N, N- dimethyl-2- [1-phenyl-1- (2-pyridyl) ethoxy] ethylamine were dissolved in a mixed solution of isopropanol 20-30 ° C and ethyl acetate (the volume ratio of 1: 1) was added with stirring 59.5g of succinic acid, warmed to 60 ° C, the reaction was stirred for 0.5 hours and then slowly cooled to 0-5 ° C, crystallization was stirred for 3-5 hours, under nitrogen in filtration, using 100ml of isopropanol and filter cake were washed with 200ml of ethyl acetate, the filter cake p> 0.08,45-50 ° C for 6-8 hours and dried under reduced pressure to yield N, N- dimethyl-2- [1 - phenyl-1- (2-pyridinyl) ethoxy] ethanamine succinate white solid 181.8g, content of 99.99percent,, the maximum absorption wavelength 262nm, 93percent yield, m.p. 105-106.5 ° C, total yield 91percent, as shown in FIG HPLC purity 99.93percent, as shown in FIG GC purity 99.90percent, MS data shown in Figure 1, MS: 271.2 [M + H]
Reference：
[1] Patent: CN103524403, 2016, B, . Location in patent: Paragraph 0055-0057
[2] Patent: CN105237467, 2016, A, . Location in patent: Paragraph 0048-0050
40
[ 110-15-6 ]
[ 676-47-1 ]
Reference：
[1] Journal of Organic Chemistry, 2014, vol. 79, # 7, p. 3152 - 3158
With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃;
To succinic acid (3 0 g, 25 42 mmol, 1 OO equiv) m THF (50 mL) was added a solution of 1- hydroxypyrrohdine-2,5-dione (64 g, 55 65 mmol, 2 20 eqmv) This was followed by the addition of a solution of DCC (11 5 g, 55 83 mmol, 2 20 equiv) in THF (50 mL) dropwise with stirring at O0C The resulting solution was stirred overnight at room temperature The reaction progress was monitored by LCMS The solids were collected by filtration and the filtrate was concentrated to give the crude product The resulting solids were washed with THF and ethanol This resulted in 2 4 g (27percent) of bis(2,5- dioxopyrrohdin-1-yl) succinate as a white solid.
Reference：
[1] Patent: WO2010/78449, 2010, A2, . Location in patent: Page/Page column 291
[2] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1980, vol. 29, # 5, p. 785 - 789[3] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1980, # 5, p. 1078 - 1081
[4] Chemical Papers, 2016, vol. 70, # 4, p. 505 - 514
[5] Patent: WO2016/205488, 2016, A1, . Location in patent: Paragraph 0264
1-(4-nitro-2-trifluoromethylphenyl)pyrrolidine-2,5-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
97%
With PPA; at 85℃; for 20h;
a) 10 g (48.51 mmol) 4-Nitro-2- (trifluoromethyl)-aniline, 5.73 g (48.51 mmol) succinic acid and 60 g polyphosphoric acid are combined and heated to 85 C under stirring for 20 h. The reaction mixture is stirred into water (500 ml), the formed precipitate is removed by filtration, rinsed with water and dried. Yield : 13.57g (97 %)
92%
With polyphosphoric acid; at 80℃; for 12h;
General procedure: A mixture of aniline (1.0 g, 10.75 mmol), succinic acid (1.26 g, 10.75 mmol) and 86%polyphosphoric acid (10 g) was heated at 80 C for 12 h. After cooling, H2O (50 ml) wasadded and the precipitate was filtered off, washed several times with H2O and dried. 1-Phenyl-pyrrolidine-2,5-dione 1b is obtained as an almost colorless solid. Yield(%) = 94.
With dihydrogen peroxide;methyltrioxorhenium(VII); In dichloromethane; water; acetonitrile; at 20℃;
Comparative examples 1 to 3: Oxidation of 5-hydroxymethyl furfural in homogeneous conditions; 5-hydroxymethyl furfural (HMF) was oxidized with 10 equivalents of hydrogen peroxide (35percent by weight in aqueous solution) in the presence of methyltrioxo rhenium in an amount of 5percent by weight of HMF, at a temperature about 200C during 24 to 48 hours, until the conversion of furfural was complete, in various solvents. The results of the reactions are summarized in Table 1 below.
With dihydrogen peroxide;methyltrioxorhenium(VII); In ethanol; water; at 20℃;
Comparative examples 1 to 3: Oxidation of 5-hydroxymethyl furfural in homogeneous conditions; 5-hydroxymethyl furfural (HMF) was oxidized with 10 equivalents of hydrogen peroxide (35percent by weight in aqueous solution) in the presence of methyltrioxo rhenium in an amount of 5percent by weight of HMF, at a temperature about 200C during 24 to 48 hours, until the conversion of furfural was complete, in various solvents. The results of the reactions are summarized in Table 1 below.
9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyphosphinyl]methoxy]propyl]adenine monosuccinate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1.05 g
In isopropyl alcohol; acetonitrile;Reflux;
To a solution of 9-[(R)-2-[[(S)-[[(S)-l-(isopropoxycarbonyl) ethyl] amino] phenoxy phosphinyl] methoxy] propyl] adenine (lgm, 0.0021 mol) in mixture of acetonitrile (20 gms)/ Isopropanol (6gms), succinic acid (0.22 gms, 0.0019 mol) was added and the reaction mixture was heated to reflux to dissolve the solids. The reaction mass was filtered in hot condition, filtrate cooled to 5°C and maintained for 16 hours. The product was isolated by filtration, rinsed with acetonitrile (6 gms), and dried to obtain 1.05 gms of succinate salt as a white crystalline powder. HPLC purity: 99.49percent The XRPD is set forth in Figure 05.
543 mg
In ethyl acetate;Reflux;
The TAF (476mg, 1.0mmol) and succinic acid (118mg, 1.0mmol) was suspended in ethyl acetate (10.0 ml of) the solution was heated at reflux until the solids dissolve,Hot filtration undissolved particles, then add the appropriate amount of n-hexane and then heated until turbidity appears still to clarify and slowly cooled to room temperature and overnight at this temperature, the product was isolated by filtration, washed with cold ethyl acetate and n-hexane (V / V = 1: 1) washed with a mixed solution, and dried in vacuo to give 534mg of a white solid powder.
In acetonitrile; at 20℃;
10 mg (0.027 mmol) of (S)-isopropyl-2-(((S)-((((R)- 1 -(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate was dissolved in 0.42 8 mL of acetonitrile. 3.3 mg (0.027 mmol) of succinic acid was dissolved in 0.8 mL of acetonitrile. Both the solutions were mixed together and the obtained solution was left at the room temperature. During slow evaporation of the solvent a white crystalline substance was separated. The crystalline product was dried in a vacuum drier (200 mBar) at the roomtemperature for 2h. Melting point: 108°C (DSC). XRPD: see Figure 19. JR spectrum: see Figure 21.
The TAF (476mg, 1.0mmol) and succinic acid (59.0mg, 0.5mmol) was suspended in acetonitrile (5.0ml) solution was heated to reflux, hot filtered undissolved particles, an appropriate amount of chloroform was added and then heated until cloudiness appears stationary and slowly cooled to clarify -5 ~ 0 , overnight at this temperature, the product is isolated by filtration, washed with cold chloroform, and dried in vacuo to give 135mg of a white solid powder.
The TAF (476mg, 1.0mmol) and succinic acid (82.6mg, 0.7mmol) was suspended in ethyl acetate (5.0ml) solution was heated to reflux, hot filtered undissolved particles, an appropriate amount of petroleum ether was added until cloudiness appears after heating to clarify and still slowly cooled to -5 ~ 0 , and overnight at this temperature, the product was isolated by filtration, washed with cold ethyl acetate and petroleum ether (V / V = 1: 1) was washed with a mixed solution and dried in vacuo to give 193mg of a white solid powder.
The TAF (476mg, 1.0mmol) and succinic acid (53.1mg, 0.45mmol) was suspended in isopropanol (5.0ml) solution was heated to reflux, hot filtered undissolved particles, an appropriate amount of diethyl ether was added until cloudy after and still further heated slowly cooled to clarify -5 ~ 0 , overnight at this temperature, the product is isolated by filtration, washed with cold diethyl ether solution was dried in vacuo to give 98.0mg of a white solid powder.
General procedure: Stage I (0144) Table 11 illustrates the selected counter ions for the salt screening of beta-GPA. Salt screening experiments were designed in 1:1.1 equivalence (eq) for beta-GPA to counter ion. [table-us-00011-en] TABLE 11 List of selected counterions beta- Counterion Counterion GPA sequence molecular Sample ID (mg) Counterion wt 2162-42-1 to 4 30 Hydrochloric 1 36.46 acid (36-38%)* 2162-42-5 to 8 30 Hydrobromic 2 80.91 acid (48%)* 2162-42-9 to 12 30 Sulfuric acid 3 98.08 (95-98%)* 2162-42-13 to 16 30 Phosphoric acid 4 98.00 (85%)* 2162-42-17 to 20 30 Methane sulfonic 5 96.11 acid (98%)* 2162-42-21 to 24 30 Maleic acid 6 116.07 2162-42-25 to 28 30 Fumaric acid 7 116.07 2162-42-29 to 32 30 Tartaric acid 8 150.09 2162-42-33 to 36 30 Ethanesulfonic 9 110.13 acid 2162-42-37 to 40 30 Ethanedisulfonic 10 190.20 acid 2162-42-41 to 44 30 Citric acid 11 192.12 2162-42-45 to 48 30 Malic acid 12 134.09 2162-42-49 to 52 30 Lactic acid 13 90.08 2162-42-53 to 56 30 Aspartic acid 14 133.1 2162-42-57 to 60 30 Succinic acid 15 118.09 2162-42-61 to 64 30 Sodium 16 40.00 hydroxide 2162-42-65 to 68 30 Potassium 17 56.11 hydroxide 2162-42-69 to 72 30 Oxalic acid 18 90.03 2162-45-1 to 4 30 Magnesium 19 58.32 hydroxide 76 salt screening experiments of beta-GPA with 19 different counter ions were set up with 30 mg of beta-GPA. Sets of four vials for each counterion were set up with four different solvents (0.3 mL): ethanol:water (9:1), isopropanol, acetone:water (9:1) and acetonitrile. (0146) Appropriate amounts of beta-GPA and the counterion were dissolved in the respective solvents and heated to 70-75 C. until dissolved. An additional 0.1 mL of water was added to the samples containing isopropanol, acetone:water (9:1) and acetonitrile. To samples containing L-aspartic acid, around 1.5 mL of water was required to dissolve the solids. After a clear solution was obtained, the samples were left for stirring at room temperature. Solids were observed in the following samples: 2163-42-4, 25, 26, 27, 28, 45 and 53 through 75. The solids were filtered and analyzed by XRPD immediately as wet sample. The samples that did not yield solids were placed in the oven at 50 C. for drying. The following samples resulted in solids after overnight drying: 2162-42-2, 1, 2, 3 and 21 through 24. The experiments with L-aspartic acid, sodium hydroxide, potassium hydroxide, and magnesium hydroxide resulted in the precipitation of either beta-GPA or the counterion. All the experimental observations were recorded after every step and are listed in Table 12. [table-us-00012-en] TABLE 12 Results of Salt screening Sample ID Counterion Solvent After 24 hours After Drying XRPD 2162-42-1 Hydrochloric EtOH:H2O (9:1) Clear Solution White Solid Pattern 1A 2162-42-2 Acid IPA Clear Solution White Solid 2162-42-3 Acetone:H2O (9:1) Clear Solution White Solid 2162-42-4 MeCN White Solid N/A 2162-42-5 Hydrobromic EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-6 Acid IPA Clear Solution Gel N/A 2162-42-7 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-8 MeCN Clear Solution Gel N/A 2162-42-9 Sulfuric Acid EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-10 IPA Clear Solution Gel N/A 2162-42-11 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-12 MeCN Clear Solution Gel N/A 2162-42-13 Phosphoric Acid EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-14 IPA Clear Solution Gel N/A 2162-42-15 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-16 MeCN Clear Solution Gel N/A 2162-42-17 Methanesulfonic EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-18 Acid IPA Clear Solution Gel N/A 2162-42-19 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-20 MeCN Clear Solution Gel N/A 2162-42-21 Maleic Acid EtOH:H2O (9:1) Clear Solution White Solid Pattern 6A 2162-42-22 IPA Clear Solution White Solid 2162-42-23 Acetone:H2O (9:1) Clear Solution White Solid 2162-42-24 MeCN Clear Solution White Solid 2162-42-25 Fumaric Acid EtOH:H2O (9:1) White Solid N/A Pattern 7A 2162-42-26 IPA White Solid N/A 2162-42-27 Acetone:H2O (9:1) White Solid N/A 2162-42-28 MeCN White Solid N/A 2162-42-29 L-Tartaric Acid EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-30 IPA Clear Solution Gel N/A 2162-42-31 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-32 MeCN Clear Solution Gel N/A 2162-42-33 Ethanesulfonic EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-34 Acid IPA Clear Solution Gel N/A 2162-42-35 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-36 MeCN Clear Solution Gel N/A 2162-42-37 Ethanedisulfonic EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-38 Acid IPA Clear Solution Gel N/A 2162-42-39 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-40 MeCN Clear Solution Gel N/A 2162-42-41 Citric Acid EtOH:H2O (9:1) Clear Solution Gel N/A 2162-42-42 IPA Clear Solution Gel N/A 2162-42-43 Acetone:H2O (9:1) Clear Solution Gel N/A 2162-42-44 MeCN Clear Solution Gel N/A 2162-42-45 L-Malic Acid EtOH:H2O (9:1) White Solid N/A Pattern 12A 2162-42-46 IPA Clear Solution Gel N/A 2162-42-47 Acetone:H2O (9:1) Clear Solution Gel N/...
Succinate Salt (0213) Around 72 g (0.55 moles) of beta-GPA was added to 400 mL of ethanol:water (9:1) in 500 mL jacketed vessel at 75 C. and a slurry was made. To this, a slurry of succinic acid, prepared by adding 71.2 g (0.6 moles) in 200 mL ethanol:water (9:1) at 65 C., was added. The temperature of the reactor was brought down to 18 C. and the reaction mixture was left for overnight stirring. Sample ID: 2162-62-1. (0214) The following day, the slurry was filtered and the solid was washed twice with 20 mL of isopropanol. The cake was placed in a vacuum oven at 45 C. for drying. Yield=101.3 g (97%). The solid was analyzed by XRPD and the formation of beta-GPA succinate (Pattern 15 A) was confirmed.
4-[3-chloro-4-(N'-cyclopropylureido)phenoxy]-7-methoxyquinoline-6-carboxamide succinate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
0.68 g
In ethanol; at 25 - 70℃; for 16h;
Succinic acid (0.15 g) was added to a mixture of <strong>[417716-92-8]lenvatinib</strong> free base (0.5 g) and ethanol (10 mL) at 70C and stirred for 1 hour at 65-70C. The reaction mixture was cooled to 25 C to 30C and then stirred for 15 hours at 25 C to 30C. The solid obtained was filtered and then washed with ethanol (5mL). The solid was dried under reduced pressure at 50C to 55C for 18 hours to obtain the title compound. Yield: 0.68 g
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